FANCL is a RING-type ubiquitin ligase that functions as a core component of the Fanconi anemia (FA) pathway, mediating monoubiquitination of FANCD2 and FANCI in partnership with the E2 enzyme UBE2T 123456. This ubiquitination represents a critical regulatory step in cellular DNA damage responses. FANCL promotes both interstrand crosslink (ICL) repair and homologous recombination (HR) at double-strand breaks (DSBs) through FANCD2-dependent mechanisms and by facilitating CtIP accumulation at DSB sites, enabling DNA end resection and Rad51 loading 7. Mutations in FANCL cause Fanconi anemia complementation group L, characterized by chr2 instability and cancer predisposition 89. Additionally, FANCL deficiency predisposes to endothelial damage and pulmonary arterial hypertension (PAH) through accumulation of DNA damage in pulmonary microvascular endothelial cells, with downregulation observed in patients with idiopathic PAH 10. FANCL mutations have also been associated with primary ovarian insufficiency, implicating FA pathway dysfunction in reproductive system development 11.