Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (By similarity). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (PubMed:17182851, PubMed:20237282). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (By similarity). Required during embryonic and postnatal retinal development (PubMed:22398208). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (PubMed:20399730, PubMed:26404741). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (PubMed:20399730). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (PubMed:20237282). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (PubMed:15234345). May play a role in the T-cell receptor-mediated activation of NF-kappa-B (By similarity). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (PubMed:15677456). Required for the normal polarized localization of the vesicular marker STX4 (PubMed:20237282). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (PubMed:21145499). Heterodimer with MPP1 (By similarity). Forms a heterotrimeric complex composed of PALS1, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (By similarity). Component of a complex composed of PALS1, CRB1 and MPP4 (By similarity). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3 (By similarity). Component of a complex composed of PALS1, CRB1 and EPB41L5 (By similarity). Within the complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain), and interacts with CRB1 (via intracellular domain) (By similarity). Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as a bridging protein between MPP3 (via guanylate kinase-like domain) and CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N-terminus) (PubMed:11927608, PubMed:12527193, PubMed:20399730). Interacts with EZR (PubMed:15677456). Interacts (via PDZ domain) with CRB1 (via C-terminal ERLI motif) (By similarity). While the PDZ domain is sufficient for interaction with CRB1, the adjacent SH3 and guanylate kinase-like domains are likely to contribute to a high affinity interaction (By similarity). Interacts with WWTR1/TAZ (via WW domain) (PubMed:21145499). Interacts with MPP7 (By similarity). Interacts (via PDZ domain) with CRB3 (via C-terminus) (PubMed:12527193). Interacts with LIN7C (PubMed:10753959). Interacts with MPDZ (PubMed:15316081). Interacts with PARD6B (PubMed:12545177, PubMed:15140881). Interacts with SC6A1 (PubMed:15234345). Interacts with CDH5; the interaction promotes PALS1 localization to cell junctions and is required for CDH5-mediated vascular lumen formation and endothelial cell (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3 domains) (By similarity). Interacts with NPHP4 (By similarity). Interacts with CRB2 (PubMed:20399730). Localized to the tight junctions of epithelial cells (PubMed:10753959, PubMed:11927608, PubMed:15140881, PubMed:15677456). Localized to the Golgi apparatus in T lymphocytes (By similarity). Localized to a subset of intracellular vesicles (PubMed:15234345). Localized to the Purkinje cell body and axon (PubMed:15234345). Localized to intercellular junctions in vascular endothelial cells (By similarity). Localized to Schmidt-Lanterman incisures, the adaxonal domain, and the inner part of paranodal loops in myelinating Schwann cells of the sciatic nerve (PubMed:20237282). Localized to apical membrane domains of the outer limiting membrane (OLM) junctions in the retina (PubMed:15558731). Colocalizes with CRB1 at the OLM, apical to the adherens junction (By similarity). Colocalizes with MPP1 in the retina at the OLM (By similarity). Colocalizes with MPP3 to the subapical region of adherens junctions in the retina OLM (By similarity). Expressed in the retinal pigment epithelium (at protein level) (PubMed:15558731, PubMed:22398208, PubMed:23893895, PubMed:26404741). Expressed in the vascular plexus of the retina (at protein level) (PubMed:27466317). In the brain, expressed in the dentate gyrus of hippocampus, striatum and cerebellum (at protein level) (PubMed:15234345, PubMed:26404741). Expressed in the sciatic nerve (at protein level) (PubMed:20237282). Expressed in the kidney nephron (at protein level) (PubMed:10753959, PubMed:15558731). Expressed in the lung, and heart (PubMed:10753959, PubMed:15558731). Expressed in placenta, brain, skeletal muscles, pancreas and liver (PubMed:10753959). Expressed in the developing sciatic nerve, with increasing expression from newborn to postnatal day 20, and decreasing expression at postnatal day 60 (P60) (at protein level) (PubMed:20237282). Expressed in the developing neural tube, optic vesicle, branchial arches and kidney at 10.5 dpc (PubMed:17920587). Expressed in the ventricular layers of the developing neural tube along the entire cranial-caudal length, including the anterior forebrain and the posterior spinal cord at 11.5 dpc (PubMed:17920587). Highly expressed in cortical progenitor cells at 12 dpc, expression decreases during neurogenesis but weak expression is still present at birth (PubMed:20399730). Expressed in the developing brain at 15.5 dpc in the upper rhombic lip, ventricular zone, and external granule layer (EGL) (at protein level) (PubMed:26657772). At birth expressed in the ventricular apical lining cells, proliferating external granule layer and Purkinje cell layer (PCL), with expression remaining abundant in the EGL and weakly evident in the PCL at P6 (at protein level) (PubMed:26657772). Expressed at P8 in the EGL, cerebellar granule neuron precursors, Bergmann glia, Pcna-positive progenitor cells in the white matter, and weakly in Pax6-positive postmitotic granule neurons (at protein level) (PubMed:26657772). Expressed weakly throughout the retina between 12.5 dpc and 14.5 dpc, becoming enriched in progenitors at the outer neuroblastic layer at 14.5 dpc (PubMed:22398208). Expressed in the retinal layer of the optic vesicle, and weakly expressed in the retinal pigment epithelium at 12.5 dpc (PubMed:17920587). Localized to the apical edge of the retina between 12.5 and 16.5 dpc (PubMed:22398208). Expressed in the internal endodermal layer and in the developing saccules of the lung at 11.5 dpc (PubMed:17920587). Expressed at the outer limiting membrane of the retina at 18.5 dpc and 3 months of age (PubMed:23001562). The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ. The PDZ domain binds to the C-terminus of SC6A1. Conditional knockout in the retina results in mice which are viable, fertile, and morphologically normal apart from microphthalmia with severe defects in visual response (PubMed:22398208). From 13.5 days post-conception (dpc) retinas show variable morphology, including retinal folding, variable thickness and disorganization (PubMed:22398208). Postnatally the retinal lamina is thinner, and disorganized, with a shortening or absence of the inner and outer segments of photoreceptor cells (PubMed:22398208). By postnatal day 60 retinas are completely or partially devoid of the outer nuclear layers and photoreceptor layer, and feature a reduced number of photoreceptor cells, disrupted cell polarity and impaired distribution of retinal neurons (PubMed:22398208). Retinal distribution of Par3 and the Crb polarity complex proteins Crbs and Patj is disrupted (PubMed:22398208). Mature mice show aberrant proliferation and apoptosis of retinal epithelia with significantly reduced or undetectable a- and b-waves in electroretinogram-measured dark-adapted response (PubMed:22398208). Conditional knockout in cerebellum proliferating progenitors at 13.5 dpc results in mislocalization of apical polarity complex proteins such as Crb proteins, Pard3, and Prkci at 15.5 dpc (PubMed:26657772). Following cerebellum conditional knockout there is an increase in migration and premature differentiation of Pax2-positive ventricular zone cells at 17.5 dpc, resulting in a reduced number of glial cell progenitors (PubMed:26657772). Conditional knockout in cerebellum results in stunted cerebellum growth and indistinct vermis foliation at birth, there is also an evident reduction of Bergmann glia, oligodendrocyte, astrocyte and GABAergic interneuron progenitors (PubMed:26657772). Conditional knockout in cerebellum shows compromised Purkinje cell migration and formation failure of Purkinje cell plate to contain both Bergmann glia and Purkinje cells, possibly as a result of abnormal Reln-Dab1 signaling at P6 (PubMed:26657772). Conditional knockout in cerebellum results in poorly layered, smaller lobes, severe defects in fissure formation and a reduced number of cerebellar granule neurons and GABAergic interneurons from P8 to P21 (PubMed:26657772). Conditional knockout in the cortex results in mice surviving to adulthood, with lower body weight but exhibit irregular movements with disrupted stride and gait, reduced exploratory initiative, reduced locomotor behavior and swim in circles (PubMed:20399730). Reduced cortical size and disrupted morphology at 12 and 14 dpc resulting in the absence of the cortex postnatally lacking virtually all cortical neurons, additionally extreme thinning of the lateral cortex is observed (PubMed:20399730). Reduced proliferation of cortical progenitor cells and increased cell death of postmitotic neurons in the developing medial cortex and ventral zone from 10.5 dpc, additionally mislocalization and reduced abundance of Crb2 and Prkci is evident (PubMed:20399730). RNAi-mediated knockdown in the sciatic nerve results in mislocalization of Exoc4/Sec8 and Stx4 in Schwann cells and thinning and shortening of Schwann cells as a result of a reduction in the myelinated fiber diameter caused by fewer myelin turns (PubMed:20237282). Conditional knockout of both Mpp3 and Pals1 in the retina results in an increase in retinal degeneration that becomes evident at one month of age (PubMed:23893895). Belongs to the MAGUK family.