Loss-of-function mutations in the gene STAR, which are associated with congenital lipoid adrenal hyperplasia (lipoid CAH), account for a small percentage of CAH in most populations, but appear to be more common in individuals of Japanese, Korean, or Palestinian ancestry (9). STAR codes for the steroid acute regulatory protein, which fulfills a gatekeeper function for all of steroid biosynthesis by catalyzing the transfer of cholesterol from the cytosol into mitochondria, where the initial steps of steroidogenesis take place. Absence of functional StAR protein reduces cholesterol import into mitochondria by a factor of about ten, leading to impaired biosynthesis of all steroids and accumulation of cholesterol lipid droplets in the cytoplasm of affected cells. However, StAR-protein independent cholesterol import may allow for enough steroid synthesis to prevent acute symptoms in the absence of functional StAR protein, and only the gradual accumulation of lipid droplets leads to complete cessation of all steroidogenesis through generalized damage to the affected cells. For this reason, defects in STAR cause damage to steroidogenic target organs such as the adrenals and the gonads only if they are stimulated to produce steroids. This “two hit” model of lipoid CAH explains why 46XY infants with lipoid CAH are born as phenotypic females, while onset of acute primary adrenal insufficiency and salt wasting may not occur until several weeks or even months after birth. The fetal testis is stimulated and thus damaged by absence of functional StAR early in gestation, leading to lack of testosterone and preventing development of male external genitalia. In the adrenals, in contrast, stimulation prior to birth affects primarily the fetal zone; the definitive zone, which postnatally develops into the zona glomerulosa and zona fasciculata, may therefore remain partially functional for several weeks or months after birth in individuals with reduced StAR-protein activity. Similarly, the ovaries in 46XX individuals remain hormonally silent until puberty, when individual ovarian follicles are stimulated and, in individuals with lipoid CAH, thus damaged during each cycle. However, while 46XX individuals with lipoid CAH can spontaneously enter puberty and may undergo menarche, their cycles remain anovulatory because lack of StAR-protein activity prevents the progesterone surge necessary for ovulation. To learn more about the genetics of CAH, please visit out CAH Overview page .