Gondadal differentiation is genetically determined in humans. Sex is determined when the bipotential embryologic tissues differentiate into testes or ovary. SRY, a gene located on the Y chromosome, triggers a complex genetic cascade leading to testicular differentiation. However, only a minority of 46, XY sex reversal patients can be explained by SRY mutations, suggesting that other genes influencing sex determination are to be discovered. Recent studies show that testis differentiation requires insulin receptor family function in mice. SRY normally requires two distinct NLS-dependent nuclear import pathways to reach sufficient levels in the nucleus for gonadal differentiation.