Colipase (CLPS) is a lipid metabolic enzyme activator localized to the extracellular region with roles in digestive lipid processing. The protein functions as an essential cofactor for pancreatic lipase, facilitating triglyceride hydrolysis in the small intestine during fat digestion. Colipase contains an N-terminal fragment called enterostatin, which acts as a satiety signal to regulate food intake and energy homeostasis. At the molecular level, colipase operates in the lipid metabolic pathway by enhancing lipase substrate accessibility and catalytic efficiency at the lipid-water interface. The clinical significance of colipase relates to digestive lipid malabsorption: pancreatic insufficiency or colipase deficiency impairs dietary fat digestion, leading to steatorrhea and nutritional deficiencies. Enterostatin derived from colipase has been investigated as a potential therapeutic target for appetite modulation and obesity management, given its demonstrated satiety-promoting properties. Genetic or acquired colipase deficiency contributes to fat-soluble vitamin malabsorption (vitamins A, D, E, K), which has systemic health implications. Understanding colipase biology is relevant for managing pancreatic disorders, cystic fibrosis-related digestive complications, and potential appetite-regulation therapies, though additional clinical research is needed to establish enterostatin's therapeutic utility.