Through its E3 ubiquitin ligase activity, MKRN3 serves as a negative regulator of GnRH secretion on the transcriptional and translational level, and MKRN3 depletion contributes to hypogonadism, infertility, and central precocious puberty (CPP) in PWS [13,21,32,33,34]. Here, GNRH1 is linked to central precocious puberty.