PUM1 is a sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by recognizing the Pumilio Response Element (PRE) in target mRNA 3′-UTRs. It mediates repression through multiple mechanisms: recruiting the CCR4-POP2-NOT deadenylase complex to promote translational inhibition and mRNA decay, and facilitating miRNA accessibility to suppress target expression. Following growth factor stimulation, phosphorylated PUM1 binds the 3′-UTR of CDKN1B/p27 mRNA, exposing miRNA-binding sites and promoting cell-cycle entry. PUM1 also regulates E2F3 and ATXN1 mRNA levels, and its activity is modulated by the lncRNA NORAD, which sequesters PUM1 to prevent repression of genomic-stability genes. Beyond cell-cycle control, PUM1 functions in spermatogenesis, stem cell differentiation, and immune sensing. Loss-of-function mutations cause neurological disease: haploinsufficiency causes Pumilio1-associated developmental disability, ataxia, and seizure (PADDAS), while milder missense variants cause adult-onset cerebellar ataxia (PRCA) 1. PUM1 also suppresses TLR4 expression in mesenchymal stem cells, protecting against aging and osteoarthritis 2, and modulates tropomyosin-4 translation via exosomes to regulate hepatic fibrosis in metabolic dysfunction-associated steatotic liver disease 3. These functions establish PUM1 as a regulatory hub for cell proliferation, differentiation, and age-related disease processes.