NCOA7 (nuclear receptor coactivator 7) is a multifunctional protein that serves as both a transcriptional coactivator and a key regulator of cellular stress responses. As a transcriptional coactivator, NCOA7 enhances the activity of nuclear receptors including ESR1, THRB, PPARG, and RARA 1. Beyond transcription, NCOA7 plays critical roles in lysosomal function and cellular homeostasis by directly binding to and inhibiting V-ATPase, the vacuolar proton pump, through its TLDc domain 23. This V-ATPase regulation maintains optimal pH in the Golgi apparatus and trans-Golgi network for proper protein glycosylation 2. NCOA7 also facilitates stress granule clearance through autophagy by partitioning into G3BP1-V-ATPase-containing stress granules 4. Disease relevance includes pulmonary arterial hypertension, where NCOA7 deficiency causes lysosomal dysfunction and inflammatory oxysterol production 5, ovarian aging through impaired stress granule clearance 4, and cancer progression, as NCOA7 acts as a tumor suppressor in clear cell renal cell carcinoma by inhibiting MAPK/ERK signaling 6. NCOA7 also provides oxidative stress protection and prevents endothelial-to-mesenchymal transition 1. These findings establish NCOA7 as a potential therapeutic target for multiple age-related diseases.