Qki, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family and the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. It plays diverse roles in regulating pre-mRNA post-transcriptional processing, intracellular migration, and mRNA stability. Qki is involved in multiple biological pathways and is of great biological importance, with its isoforms QKI-5, QKI-6, and QKI-7 having distinct functions in a cell-type-specific manner [5].

In various studies, gene knockout models have provided insights into Qki's functions. In lens-specific Qki-deficient mice, genes associated with cholesterol biosynthesis were downregulated, leading to a reduced cholesterol level in the eye lens, protein aggregate accumulation, and eventually cataracts. This shows Qki is required for the transcriptional activation of cholesterol biosynthesis genes in the eye lens [1]. In neonatal mice with Qki depletion in neural stem cells or oligodendrocyte precursor cells, cholesterol biosynthesis was impaired, resulting in defective myelinogenesis, highlighting Qki-Srebp2-controlled cholesterol biosynthesis as essential for myelinogenesis [2]. In microglia, deletion of the Qk gene severely impaired the clearance of myelin debris, indicating Qki is an essential regulator of microglial phagocytosis in demyelination [4]. In BMSCs-specific QKI-deficient mice, an increase in bone mass was observed, with promoted osteogenic differentiation, suggesting QKI suppresses osteogenic differentiation of BMSCs [3].

In conclusion, Qki is crucial for maintaining the cholesterol level in the eye lens to prevent cataracts, for myelinogenesis in the central nervous system, for microglial phagocytosis during demyelination, and for regulating osteogenic differentiation in bone marrow-derived mesenchymal stem cells. The study of Qki using gene knockout mouse models has significantly contributed to understanding its role in these biological processes and related diseases, such as cataracts, demyelinating diseases, and osteoporosis.