GDF3 (growth differentiation factor 3) is a TGF-β superfamily cytokine with critical roles in metabolic regulation and inflammatory responses. The protein functions as a signaling molecule that regulates adipose tissue homeostasis and lipid metabolism through receptor complexes including ALK5, ALK7, ACVR2A, and ACVR2B 1. GDF3 promotes lipolysis in mature adipocytes by enhancing β3-adrenergic receptor signaling and cAMP-PKA pathways 1. The protein exhibits pro-inflammatory effects, particularly during aging, where it maintains macrophage inflammatory phenotypes through autocrine GDF3-SMAD2/3 signaling 2. This mechanism involves chr12 remodeling that shifts adipose tissue macrophages toward an inflammatory state by limiting methylation-dependent chr12 compaction 2. In disease contexts, GDF3 contributes to insulin resistance and metabolic dysfunction, with PPARγ S273 phosphorylation promoting GDF3 expression and subsequent diabetogenic effects 3. The protein also serves as a biomarker for cardiac pathology, with elevated circulating GDF3 levels predicting adverse fibrotic remodeling after myocardial infarction 4. Additionally, GDF3 variants have been implicated in congenital developmental disorders, including congenital scoliosis, where certain mutations show pathogenic effects in functional assays 5.