The nucleosome assembly protein 1 like 1: From histone chaperone to disease regulator

Nucleosome assembly protein 1-like 1 (NAP1L1), a canonical member of the NAP1 family, orchestrates chromatin architecture and nucleosome dynamics to regulate cell cycle progression, development and proliferation. NAP1L1 is mainly expressed in actively growing cells, and its dysregulation is closely associated with the occurrence of a variety of diseases, including neurodevelopmental disorders, cardiovascular diseases and cancers. Recent studies have revealed that NAP1L1 can influence disease progression by modulating multiple classic signaling pathways such as cGAS-STING, PI3K/AKT and WNT pathways, highlighting its complex involvement in cellular signaling networks. In this review, we systematically summarized the discovery, structural features, and multifaceted biological functions of NAP1L1, with a particular focus on its pathogenic roles in cancer and cardiovascular diseases. We evaluated its potential as a druggable target by integrating computational biology approaches with structural and pharmacological evidence, identifying conserved ligandable pockets and predicting plausible interactions with known bioactive compounds. These findings position NAP1L1 as a potential druggable target with promising prospects at the intersection of chromatin plasticity and signal transduction, and provide comprehensive insights into the therapeutic potential of targeting NAP1L1, providing information and advancement for future clinical strategies.