 These fibroblasts fill with immunoreactive large vacuoles; but more importantly their abnormal concentration of PI(3,5)P2 demonstrates conserved function of mammalian FIG4 and late endosome-lysosome axis failure responsible for lack of apoptosis of neurons and Schwann cells (but large motor axons are still lost while demyelination still happens).In contrast, homozygous FIG4 defective (FIG4-/-) mice have a reduction of myelin, especially in optic nerves; but this detriment is rescued by an overexpression of human FIG4 I41T at low-level function.While FIG4-null adult mice have macroscopically normal brains with increments in apoptosis and neuronal density with delayed cell maturation, neonatal mice maintain all neurologic defects.