FAM32A is a metazoan-specific, intrinsically disordered protein essential for pre-mRNA splicing and cell cycle regulation. In the spliceosome, FAM32A functions as a step II exon ligation factor that directly bridges the 5'-exon and intron 3' splice site to promote exon ligation during the C-to-C* transition 12. FAM32A stabilizes the catalytic conformation alongside other metazoan factors (CACTIN, SDE2, NKAP), enabling fine-tuning of alternative splicing 1. Beyond splicing, FAM32A modulates the G1/S cell cycle transition by regulating CDKN1A splicing; Mettl14 deficiency stabilizes FAM32A mRNA through m6A modifications, elevating FAM32A protein and accelerating G1/S progression 3. Depletion of FAM32A leads to increased intron retention and downregulation of essential genes, compromising cellular viability 4. Clinically, low FAM32A expression associates with poor prognosis in gastric cancer and reduced chemosensitivity; FAM32A-suppressed cells show resistance to 5-fluorouracil through decreased p53 pathway activation and impaired apoptosis 5. FAM32A methylation also associates with cognitive function, suggesting broader epigenetic roles 6. These findings establish FAM32A as a multifunctional tumor suppressor linking splicing regulation to cell cycle control and chemotherapy response.