KLC4 (kinesin light chain 4) is a microtubule-associated motor protein that functions as a light chain component of the kinesin complex, mediating cargo coupling to the heavy chain and regulating ATPase activity 1. In normal physiology, KLC4 supports intracellular transport and organelle trafficking through microtubule-based movement 1. KLC4 mutations cause hereditary spastic paraplegia (HSP), a neurodegenerative disorder. A 19 bp deletion in exon 6 generates a truncated protein and causes autosomal-recessive spastic paraplegia with progressive neurological decline 2. Heterozygous variants can lead to late-onset autosomal-dominant HSP, as demonstrated in humanized C. elegans models showing nuclear migration defects correlating with clinical severity 3. Beyond neurodegeneration, KLC4 is upregulated in lung and cervical cancers and promotes radioresistance through mitochondrial protection. KLC4 depletion induces apoptosis via mitochondrial dysfunction, increased reactive oxygen species, and calcium influx 1. KLC4 also confers chemoresistance through CHK2-mediated DNA damage response inhibition 4. Notably, SETD3-mediated KLC4 downregulation restores radiosensitivity in cervical cancer 5. Additionally, KLC4 dysregulation associates with depression-like phenotypes through impaired synaptic plasticity 6. These findings suggest KLC4 is a therapeutic target for both neurodegeneration and cancer resistance.