NCOA3 (nuclear receptor coactivator 3) is a transcriptional coactivator that directly binds nuclear receptors and enhances their hormone-dependent transcriptional activity. NCOA3 functions by assembling multisubunit coactivator complexes and remodeling chr20 through its histone acetyltransferase activity, facilitating coactivation of diverse nuclear receptors including estrogen receptor (ER), glucocorticoid receptor (GR), retinoic acid receptors (RARs/RXRs), thyroid hormone receptors (TRs), vitamin D receptor (VDR), and PPARs 1. Additionally, NCOA3 participates in NF-κB pathway coactivation 2. NCOA3 displays critical roles across multiple disease contexts. In diabetic kidney disease, NCOA3 deficiency impairs podocyte autophagy via reduced Fyn transcription through PPAR-γ-dependent mechanisms, with NCOA3 overexpression protective against high glucose-induced injury 3. In breast cancer, NCOA3 amplification (known as AIB1) acts as an oncogene driving tumor progression and endocrine therapy resistance through both ER-dependent and independent mechanisms 1. NCOA3 also functions in metabolic reprogramming; PFKFB4-mediated phosphorylation of NCOA3 enhances its transcriptional activity to promote glucose metabolism and aggressive breast cancer phenotypes 4. In hepatocellular carcinoma, cytosolic NCOA3 stabilization supports macropinocytosis-dependent albumin uptake and cellular migration 5. NCOA3 is implicated in osteoarthritis genetic susceptibility 6 and in human embryonic development, where its knockdown delays development and correlates with pluripotency maintenance 7. Clinically, NCOA3 represents a therapeutic target whose modulation could address cancer progression, metabolic disease, and developmental disorders.