DIP2A (DIP2 acetate-CoA ligase A) is a multifunctional protein that serves as a cell surface receptor for follistatin-like protein 1 (FSTL1) and plays critical roles in cellular metabolism and signaling. Upon FSTL1 binding, DIP2A activates multiple downstream pathways including AKT and P38 MAPK signaling 1. The protein catalyzes acetyl-CoA synthesis and promotes protein acetylation, contributing to dendritic spine morphology and synaptic transmission. Mechanistically, DIP2A mediates FSTL1-induced cellular responses through the DIP2A-P38 pathway, regulating NCOA4 expression and subsequent ferritinophagy in immune cells 1. DIP2A demonstrates significant disease relevance across multiple conditions. In cancer, the FSTL1-DIP2A axis promotes immune evasion by inducing NK cell ferroptosis in gastric cancer 1 and serves as a poor prognostic biomarker for anti-PD1 therapy efficacy 2. The protein is involved in metabolic liver diseases through the IRF4-FSTL1-DIP2A/CD14 signaling pathway in nonalcoholic steatohepatitis 3. Additionally, genetic variants in DIP2A are associated with developmental dyslexia in Chinese populations 4, and autoantibodies against DIP2A have been identified in autoimmune hepatitis patients 5, suggesting broad clinical significance in neurodevelopmental, metabolic, and autoimmune disorders.