Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). Interacts with RHBG and SPTBN1 (PubMed:15262991, PubMed:15611082). Colocalizes with Na/K ATPase, Na/Ca exchanger and SPTBN1 (PubMed:19007774). Directly interacts with DMD; this interaction is necessary for DMD localization at the sarcolemma. Interacts with DCTN4; this interaction is required for DCTN4 retention at costameres. Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (By similarity). Interacts (via death domain) with RABGAP1L (via Rab-GAP TBC domain) (PubMed:27718357). Expressed at the apical membrane of airway lung epithelial cells (By similarity). Localized to the plasma membrane of the inner segments of photoreceptors in retina. Colocalizes with SPTBN1 in a distinct intracellular compartment of neonatal cardiomyocytes (PubMed:19007774). In skeletal muscle, localizes to neuromuscular junctions (By similarity). Localizes with puncta at mitochondria ends. Colocalizes and cotransports on motile vesicles with RABGAP1L (By similarity). Present in plasma membrane of neurons as well as glial cells throughout the brain. Expressed in fetal brain and in temporal cortex of adult brain. Also expressed in the inner segments of rod photoreceptors in retina. The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin. Phosphorylated at multiple sites by different protein kinases and each phosphorylation event regulates the protein's structure and function. The disease is caused by variants affecting the gene represented in this entry. CDS lacks C-terminal region which is nevertheless present in the underlying cDNA. Ankyrin entry