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Insulin-like 3 and its receptor, leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8), are essential for the first phase of testicular descent. Homozygous loss of either of the two genes in mice leads to cryptorchidism. Although mutations in both homologous human genes are not a common cause of cryptorchidism. To date, only one missense mutation at codon 222 (T222P) of the LGR8 gene has been proposed as a causative mutation for cryptorchidism. This conclusion was based on both functional in vitro studies and the lack of mutation in a large group of controls. The geographical origin of the mutation carriers suggested a founder effect in the Mediterranean area.

The Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 8 Gene T222P Mutation Does Not Cause Cryptorchidism