The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and thus inhibiting the JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response (By similarity). Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells (PubMed:23963642). Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAP2K7/MKK7, MAP3K11/MLK3 and DLK1. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2) (By similarity). Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP (By similarity). Interacts, via the PID domain, with ARHGEF28. Interacts with MAP3K7/TAK1 and VRK2 (By similarity). Interacts with DCLK2 (PubMed:16628014). Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642). Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Interacts with SH3RF2 (By similarity). Accumulates in cell surface projections. Under certain stress conditions, translocates to the perinuclear region of neurons. In insulin-secreting cells, detected in both the cytoplasm and nucleus (By similarity). Expressed predominantly in the brain and insulin-secreting cells. In the brain, high expression found in the cerebral cortex and hippocampus. Localizes in the synaptic regions of the olfactory bulb, retina, cerebral and cerebellar cortex and hippocampus. Also expressed in a restricted number of axons, including mossy fibers from the hippocampal dentate gyrus, soma, dendrites and axons of cerebellar Purkinje cells. Also expressed in kidney, testis and prostate. Low levels in heart, ovary and small intestine. Isoform JIP-1b is more predominant in the brain than isoform JIP-1a. Isoform Jip1-a is expressed both in the brain and kidney, isoform JIP-1c, isoform JIP-1d and isoform JIP-1e are brain specific. Low levels at prenatal stage 15 dpc, increased levels during the first postnatal days, with a plateau at postnatal day 15. Upon neuron differentiation. The SH3 domain mediates homodimerization. Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by VRK2. Hyperphosphorylated during mitosis following activation of stress-activated and MAP kinases (By similarity). Ubiquitinated. Two preliminary events are required to prime for ubiquitination; phosphorylation and an increased in intracellular calcium concentration. Then, the calcium influx initiates ubiquitination and degradation by the ubiquitin-proteasome pathway. Belongs to the JIP scaffold family.