Huntingtin-interacting protein 1-related protein

Huntingtin-interacting protein 1-related protein (HIP1R) is an endocytic adaptor that links clathrin-coated pits and vesicles to the actin cytoskeleton (UniProt: O75146). It contains an ENTH domain that binds 3-phosphoinositides and may promote cell survival by stabilizing receptor tyrosine kinases after ligand-induced endocytosis. The protein functions in vesicular trafficking and membrane dynamics, processes critical for neuronal signaling.

HIP1R localizes to multiple subcellular compartments and participates in clathrin-mediated endocytosis, a fundamental process in synaptic transmission and cell surface receptor regulation. No disease associations are documented in UniProt, though the protein's role in endocytic trafficking suggests relevance to cellular stress responses and protein homeostasis.

In Alzheimer's disease, HIP1R is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC = −0.56; Chaparral AD proteomics). This reduction was observed across subcellular fractions in TMT-labeled quantitative proteomic analysis of human brain. Reduced HIP1R levels may impair endocytic recycling of receptors and contribute to synaptic dysfunction in AD pathology.