Regulatory network analysis revealed HMGCS1 as a novel IPF-associated gene interacting with PPARα signaling, while SOCS3 coordinated multiple hub genes (IL6, CEBPD, UCP2, and CFH) through FOXA1/2-mediated transcriptional regulation alongside JAK/STAT3 pathway suppression. Here, HMGCS1 is linked to idiopathic pulmonary fibrosis.