GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE278nnn/GSE278954/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278954GEOGSEfalseLiver Disease Reveals KIF12 as a Critical Regulator of Organelle LocalizationKinesin family member 12 (KIF12) has been implicated in liver disease requiring transplantation in pediatric patients. Single cell RNA-sequencing shows KIF12 expression selectively in biliary cells in healthy human liver. Here, we generated a human KIF12-disease model by introducing a homozygous KIF12 p.Arg219* mutation in induced pluripotent stem cells. These cells were differentiated into 2D cholangiocyte-like cells (iCCs) and 3D biliary organoids. Pioneering single-molecule fluorescence microscopy in live iCCs, we observed wild-type KIF12 co-localizing with microtubules, consistent with prediction of being a microtubule associated motor protein. KIF12 deficiency causes perinuclear clustering of mitochondria and lysosomes, along with aberrant cilia localization. These defects were rescued by viral delivery of wild-type KIF12. Collectively, these findings uncovered a mechanistic link between KIF12 dysfunction, mitochondria, lysosomes, and cilia mispositioning, and biliary pathology. Our study expands the knowledge of kinesins beyond neuronal function and provides a foundation for development of targeted genetic therapies for kinesinopathies.2026/09/23GSE278954GSM8558815GSM8558814GSM8558823GSM8558819GSM8558818GSM8558817GSM8558816GSM8558822GSM8558821GSM855882024676278954Homo sapiens[42727250]