HNRNPK is a major pre-mRNA-binding protein that binds tenaciously to poly(C) sequences and plays multifaceted roles in RNA metabolism and transcriptional regulation. 1 Mechanistically, HNRNPK functions as a transcriptional coactivator of p53 when sumoylated, regulating p21 and 14-3-3 sigma induction, while also mediating p53-dependent apoptosis through interaction with lincRNA-p21. 1 Beyond p53 signaling, HNRNPK participates in alternative splicing regulation in prostate cancer through FOXA1-mediated control and impacts the splicing landscape of oncogenic genes. 2 HNRNPK demonstrates critical roles in cellular communication and chr9 biology. It is actively packaged into extracellular vesicles through LC3-conjugation machinery, facilitating RNA sorting and secretion. 3 During X chromosome 9, HNRNPK interacts with Xist lncRNA to mediate gene silencing through liquid-liquid phase separation, concentrating silencing factors on the chr9. 4 In cancer contexts, HNRNPK promotes primary liver cancer development by stabilizing YAP downstream of TNFR2 signaling in hepatic progenitor cells, with elevated expression correlating to poor prognosis. 5 Clinically, HNRNPK mutations are associated with Au-Kline syndrome and constitute a significant component of neurodevelopmental disorders. 6 Rare deleterious variants in HNRNPK and related hnRNP genes cause shared neurodevelopmental phenotypes linked to disrupted cerebral cortical development.