Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the

Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, microtubule organizing center, centrosomeChromosome, centromere, kinetochoreCytoplasm, cytoskeleton, spindleCleavage furrowCytoplasmic vesicle membrane

Lissencephaly 4 with microcephaly

A neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly, and profound intellectual disability.

Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule

CytoplasmCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindle poleCytoplasm, cytoskeletonCytoplasm, cytoskeleton, spindle

Lissencephaly 6, with microcephaly

A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS6 features include hypoplasia of the corpus callosum, severe microcephaly and developmental delay.

Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment. Regulates microtubule function in neurons and neuronal migration. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation. Affects migration of sympathetic preganglionic neurons in the spinal

Secreted, extracellular space, extracellular matrix

Lissencephaly 2

A classic type lissencephaly associated with ataxia, intellectual disability, seizures and abnormalities of the cerebellum, hippocampus and brainstem.