Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by chronic inflammation and excessive extracellular matrix deposition, with fibrocytes playing a pivotal role in fibrotic remodeling. This study aimed to identify upstream molecular mechanisms regulating fibrocyte recruitment and activation, focusing on the pathway as a potential therapeutic target. We utilized Mendelian Randomization and phenome-wide association analyses on genes involved in sphingolipid metabolism to identify potential regulators of idiopathic pulmonary fibrosis (IPF). A bleomycin-induced mouse model was employed to examine the role of the axis in fibrocyte recruitment, using SKI-349 to target and FTY720 to antagonize . Our analyses revealed as a significant genetic driver of IPF. Targeting and S1PR1 led to a marked reduction in fibrocyte accumulation, collagen deposition, and histopathological fibrosis. Additionally, PAXX and RBKS were identified as downstream effectors of . Our protein-protein interaction mapping indicated potential therapeutic synergies with existing anti-fibrotic drug targets. Our findings establish the axis as a key regulator of fibrocyte-mediated pulmonary fibrosis and support as a promising therapeutic target.