HIP1

HIP1 (huntingtin-interacting protein 1) is a conserved eukaryotic protein encoded by the HIP1 gene. It was originally identified by its interaction with the Huntington disease protein (huntingtin) and is widely expressed in many tissues. HIP1 functions at the interface of membrane trafficking and the actin cytoskeleton.

Structurally, HIP1 contains an N-terminal ANTH-like domain that binds phosphoinositides and membranes, a central coiled-coil region that mediates protein–protein interactions, and motifs that interact with clathrin and other endocytic components. These features enable HIP1 to associate with clathrin-coated pits and vesicles and to influence endocytic uptake and vesicle trafficking.

Functionally, HIP1 acts as an adaptor or scaffolding protein in clathrin-mediated endocytosis, linking membrane curvature and cargo internalization to actin dynamics. It has been reported to modulate receptor internalization (including growth factor receptors), cytoskeletal organization, and cellular signaling pathways. HIP1 also binds to huntingtin and other intracellular proteins, and its interaction with mutant huntingtin has been proposed to contribute to altered trafficking and neuronal dysfunction.

Clinically, altered HIP1 expression has been observed in several cancers, and it has been investigated as a potential biomarker and contributor to tumorigenesis. In neurodegenerative disease research, changes in HIP1 function or localization are studied for their possible roles in Huntington disease pathophysiology. Ongoing studies continue to clarify HIP1’s molecular mechanisms and its relevance to human disease.