KIF5

KIF5 refers to a family of conventional kinesin heavy chains in humans, comprising KIF5A, KIF5B, and KIF5C. These motor proteins form the core of kinesin-1 and drive microtubule-based transport toward the plus ends of microtubules, supporting cargo movement within the cytoplasm, neurons, and other cell types. Their activity underpins fast axonal transport, organelle distribution, and intracellular trafficking essential for cell function and development.

Structural features include an N-terminal motor domain that binds and hydrolyzes ATP to generate force, a coiled-coil stalk that enables dimerization, and a C-terminal tail that mediates cargo binding through associations with kinesin light chains (KLC1-4) and various adapter proteins. Cargo specificity is achieved through interactions with adaptors such as Milton/Miro for mitochondria and JIP family proteins for vesicular cargo. Regulation occurs via autoinhibition of the motor that is relieved upon cargo binding or post-translational modifications, allowing controlled activation of transport.

Expression patterns vary among paralogs: KIF5A is enriched in neurons and is particularly associated with neuronal cargo transport; KIF5B is more broadly expressed; KIF5C is preferentially found in the brain. Together, KIF5 proteins participate in transporting mitochondria, synaptic vesicle precursors, receptors, and other organelles, contributing to neuronal development, maintenance, and overall cellular organization.

Clinical significance is observed when KIF5A harbors pathogenic variants, which have been linked to hereditary sensory and autonomic neuropathy type I (HSAN I) and spinocerebellar involvement such as SPG10; other KIF5A variants have been reported in various neurodevelopmental and neurodegenerative contexts. Disruption of KIF5-mediated transport is implicated in diseases characterized by impaired axonal transport and neuronal integrity.