PPAN (Peter Pan homolog) is a nucleolar protein essential for ribosome biogenesis, specifically required for 45S rRNA maturation and large subunit precursor processing 1. Beyond its canonical ribosomal function, PPAN localizes to both nucleoli and mitochondria, where it plays critical roles in cellular homeostasis 2. PPAN functions as an anti-apoptotic factor that inhibits mitochondrial apoptosis through p53-independent mechanisms by interacting with nucleophosmin and preventing BAX stabilization 1. Loss of PPAN triggers nucleolar stress responses, impairs mitochondrial integrity and ATP production, and enhances autophagic flux through Parkin-mediated mitophagy 2. In cancer biology, PPAN is a critical node in the NAT10-regulated DNA damage repair pathway; NAT10-catalyzed ac4C modifications enhance PPAN translation, and elevated PPAN expression promotes colorectal cancer progression and genomic stability 3. PPAN expression is co-regulated with nearby genes including P2RY11 and EIF3G, with genetic variants in this locus associated with narcolepsy susceptibility 4. These findings establish PPAN as a multifunctional regulator linking ribosome biogenesis to mitochondrial homeostasis, apoptosis evasion, and cancer cell survival.