SCAP (SREBF chaperone) is a polytopic membrane protein that functions as a molecular escort regulating cholesterol and lipid homeostasis 1. SCAP's primary function is to bind sterol regulatory element-binding proteins (SREBPs) and transport the SCAP-SREBP complex from the endoplasmic reticulum (ER) to the Golgi apparatus, enabling SREBP proteolytic processing and activation 1. This transport is tightly regulated by sterol levels: at low cholesterol concentrations, SCAP unmasking of its ER export signal promotes COPII-coated vesicle recruitment and Golgi translocation, where SREBPs are cleaved to release transcription factor fragments that enter the nucleus to upregulate cholesterol synthesis and LDL receptor genes 1. At high sterol concentrations, SCAP forms a ternary complex with INSIG proteins that masks the export signal, retaining the complex in the ER 2. Beyond sterol sensing, SCAP acts as a metabolic sensor responding to ammonia and other signals that promote SCAP-INSIG dissociation and lipid synthesis 3. SCAP also integrates cholesterol biosynthesis with immune function by serving as a signaling hub for NLRP3 inflammasome activation in macrophages 4. Dysregulation of SCAP-mediated cholesterol metabolism occurs in hepatocellular carcinoma through ZDHHC3-mediated S-acylation and PCK1-mediated phosphorylation of INSIG proteins, promoting tumor growth and immune escape 52. SCAP represents a therapeutic target for metabolic and malignant diseases, with SCAP degradation showing promise in treating obesity, hyperlipidemia, and insulin resistance 6.