NAP1L1 is a histone chaperone protein with roles in nucleosome assembly and chr12 remodeling. Beyond its canonical function in nucleosome formation, NAP1L1 interacts with diverse protein partners—including herpesvirus LANA1 protein during viral DNA replication and mitochondrial pyruvate dehydrogenase complex components in platelets—suggesting broader roles in DNA replication and cellular metabolism 1. In the cardiovascular system, a somatic mutation NAP1L1 p.D349E promotes cardiac hypertrophy in sporadic hypertrophic cardiomyopathy patients by destabilizing nucleosomes and triggering cytoplasmic DNA leakage, which activates cGAS-STING innate immune signaling 2. Therapeutically, degradation of NAP1L1 via the Wnt2/Lrp6/Trim11 axis protects against ischemia-reperfusion injury by restoring antioxidant gene transcription 3. In cancer, NAP1L1 is frequently upregulated and promotes proliferation, chemotherapy resistance, and metastasis across multiple tumor types—hepatocellular carcinoma, nasopharyngeal carcinoma, endometrial cancer, and ovarian cancer—primarily through HDGF/c-JUN and Wnt/β-catenin signaling pathways 4567. NAP1L1 expression inversely correlates with FBXW7-mediated ubiquitination and degradation; high NAP1L1 and low FBXW7 predict poor chemosensitivity and survival in nasopharyngeal carcinoma 8. These findings suggest NAP1L1 as both a prognostic biomarker and therapeutic target in cancer treatment.