HIP1R (huntingtin-interacting protein 1-related) is a multi-domain protein that functions as a component of clathrin-coated pits and vesicles, linking endocytic machinery to the actin cytoskeleton 1. The protein binds 3-phosphoinositides through its epsin N-terminal homology (ENTH) domain and stabilizes receptor tyrosine kinases by prolonging their half-life following ligand-induced endocytosis 2. HIP1R and its homolog HIP1 compensate for one another physiologically; double knockout mice exhibit dwarfism, severe vertebral defects, and early lethality, indicating HIP1R is necessary for maintaining diverse adult tissues 3. In disease contexts, HIP1R expression patterns serve diagnostic purposes in IDH-mutant gliomas, where high HIP1R levels correlate with oligodendrogliomas (1p/19q-codeleted), enabling 100% specificity in tumor classification 4. In pancreatic cancer, HIP1R acts as a tumor suppressor; its downregulation through DNA methylation and miR-92a-3p-mediated repression promotes cancer progression via PI3K/AKT pathway activation 5. Recently, HIP1R was identified as essential for MS1-96-induced PD-L1 degradation in colorectal cancer, enhancing antitumor immunity 6. Additionally, HIP1R regulates rheumatoid arthritis synovial fibroblast invasiveness and migration, implicating it in joint damage pathology 7.