KIF5A is a microtubule-dependent motor protein essential for axonal transport in neurons 1. As a plus-end-directed kinesin, KIF5A mediates anterograde transport of multiple cargo types, including neurofilament proteins, mitochondria, and SFPQ-associated RNA granules in mature motor neurons 2. KIF5A functions in complex with ZFYVE27 to facilitate vesicular transport of proteins including VAPA, VAPB, and RAB11 family members, contributing to axon elongation and guidance. Additionally, KIF5A regulates axonal repair capacity following injury 2. KIF5A mutations cause a spectrum of neurodegenerative diseases determined by mutation location and functional consequence 3. N-terminal motor domain mutations cause hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth disease type 2, while C-terminal cargo-binding domain mutations predominantly cause amyotrophic lateral sclerosis (ALS) 3. Notably, ALS-associated loss-of-function mutations confer extended survival compared to typical ALS 3. CMT and ALS mutants show impaired autoinhibition and mitochondrial distribution defects, while some ALS variants form toxic p62-positive inclusions 4. KIF5A variants account for >1% of hereditary spastic paraplegia cases 5, making targeted genetic screening clinically relevant for diagnosis.