NAP1L1 (nucleosome assembly protein 1 like 1) is a multifunctional protein with diverse roles beyond its classical nucleosome assembly function. Primarily, NAP1L1 functions as a histone chaperone involved in nucleosome assembly and chr12 remodeling 1. However, recent evidence reveals NAP1L1 performs critical roles in cytoplasmic contexts: it acts as a microtubule-associated protein regulating microtubule bundling and cell migration 2, and interacts with mitochondrial pyruvate dehydrogenase components to influence cellular respiration and thrombopoiesis 3. NAP1L1 has significant disease relevance in cancer and cardiac pathology. In hepatocellular carcinoma, elevated NAP1L1 promotes cell proliferation, chemotherapy resistance, and poor prognosis through multiple mechanisms including BIRC2 ubiquitination regulation 45. In nasopharyngeal carcinoma, NAP1L1 degradation by FBXW7 enhances cisplatin chemosensitivity by disrupting HDGF-p62 signaling and promoting autophagy 6. Somatic NAP1L1 mutations cause cardiac hypertrophy through defective nucleosome assembly, triggering cGAS-STING immune signaling and DNA cytoplasmic leakage 1. Conversely, Wnt2-mediated NAP1L1 degradation provides cardioprotection against ischemia-reperfusion injury via ROS reduction 7. Clinically, NAP1L1 represents a therapeutic target, with its inhibition showing promise for improving chemosensitivity and cardiac outcomes.