SGIP1 is a key endocytic adaptor protein that regulates clathrin-mediated endocytosis through multiple mechanisms. It functions as a membrane-binding and tubulating protein that recruits essential components for clathrin-coated pit formation, with preference for phosphatidylserine and phosphoinositide-enriched membranes 1. SGIP1 dimerizes via intermolecular disulfide bonds in its μHD domain, a critical structural feature for endocytic function 2. Beyond canonical endocytosis, SGIP1 promotes axonal surface expression of cannabinoid receptor 1 by binding its H9 domain, regulating presynaptic neuromodulation 3. Dysfunction of SGIP1 has significant clinical implications. Loss-of-function mutations cause early-onset autosomal recessive parkinsonism with associated intellectual and cognitive dysfunction, characterized by synaptic proteostasis defects, dopaminergic synapse loss, and accumulation of degradative organelles 4. SGIP1 represents one of five newly identified genes contributing to early-onset Parkinson's disease with atypical presentations 5. Additionally, SGIP1 variants associate with altered P300 electroencephalographic responses in alcohol dependence 6, and genome-wide studies link SGIP1 polymorphisms to QT interval variation, a cardiac electrophysiological trait 7. In thyroid cancer, SGIP1 expression is negatively regulated by miR-146b-5p and suppresses tumor progression 8.