PAN2 is the catalytic subunit of the PAN2-PAN3 deadenylation complex, one of two major cytoplasmic mRNA deadenylases responsible for poly(A) tail shortening 1. PAN2 catalyzes 3'-5' exonucleolytic degradation of mRNA poly(A) tails in a manner stimulated by poly(A)-binding protein (PABPC1) 2, with activity on long poly(A) tails characteristic of mammalian mRNAs 2. This deadenylation represents the rate-limiting and often initial step in mRNA degradation across multiple decay pathways 3. Following PAN2-mediated shortening, the CCR4-NOT complex continues degradation, with deadenylated mRNAs subsequently degraded via exosome-mediated or decapping-dependent pathways 1. PAN2 also facilitates mRNA processing body (P-body) formation and function, playing structural and functional roles beyond substrate preparation 4. Beyond canonical deadenylation, PAN2 possesses deubiquitinase activity and regulates HIF1A mRNA stability during hypoxic response independent of poly(A) tail modulation. Disease associations include skeletal dysplasia, where PAN2 variants are proposed as candidate disease genes 5, and bladder cancer, where PAN2 (also designated USP52) modulates ferroptosis susceptibility through xCT protein stability regulation 6.