GSAP (gamma-secretase activating protein) is a selective modulator of γ-secretase activity that specifically enhances amyloid-β (Aβ) production without affecting other γ-secretase substrates like Notch 1. The protein derives from a larger 98 kDa precursor through caspase-3-mediated cleavage, generating a biologically active 16 kDa C-terminal fragment (GSAP-16K) 2. GSAP-16K undergoes phase separation and forms cellular condensates that modulate APP-C99 cleavage, with dilute phase promoting Aβ42 production while condensates sequester substrate 3. The protein directly interacts with APP-C99 fragments, particularly binding to amino acids 719-743 with high affinity (Kd = 0.136 μM) 4. Beyond amyloid processing, GSAP regulates lipid homeostasis and mitochondrial function through its enrichment in mitochondria-associated membranes (MAM) and interaction with the Fe65-APP complex 5. GSAP is degraded via the ubiquitin-proteasome system with a half-life of approximately 5 hours 6. Genetic variants in the GSAP promoter correlate with brain expression levels and Alzheimer's disease risk, particularly in APOE4 non-carriers 1. These findings establish GSAP as a critical regulator of amyloidogenic processing and a potential therapeutic target for Alzheimer's disease.