Klc2, the light chain of kinesin-1, is crucial for mediating cargo binding and regulating kinesin-1 motility. It is involved in the transport system of cochlear hair cells and is associated with membrane trafficking pathways. Kinesin-1, with Klc2 as its light chain, transports numerous cellular cargos via the microtubule network in the cytoplasm, playing an important role in various biological processes [1,3,5,6].

In mice, Klc2-deficient models suffer from low-frequency hearing loss as early as 1 month of age. The deficiency leads to abnormal mitochondrial transport and down-regulation of the GABAA receptor family in cochlear hair cells. Whole-genome sequencing of patients also indicates that KLC2 is related to low-frequency hearing in humans. Adeno-associated virus-mediated delivery of wild-type Klc2 cDNA sequence to Klc2-null mice shows apparent recovery, including decreased ABR threshold and reduced outer hair cell loss [1]. In zebrafish, knockdown and overexpression of klc2 reveal a mild to severe curly-tail phenotype, suggestive of a neuromuscular disorder [2]. In non-small cell lung cancer (NSCLC), down-regulation of KLC2 can promote radiosensitivity by activating the P53 pathway, and HuR-KLC2 forms a positive feedback loop that decreases p53 phosphorylation and weakens radiosensitivity [4].

In conclusion, Klc2 is essential for cochlear function in mice and humans, as demonstrated by gene-knockout models. These models have also revealed its potential roles in neuromuscular disorders and NSCLC radiotherapy resistance, highlighting the importance of Klc2 in understanding the mechanisms of related diseases and developing potential therapeutic strategies.