Adgrg2, also known as GPR64 and HE6, is an adhesion G protein-coupled receptor that is essential for maintaining male fertility [1]. It is involved in regulating ion/pH homeostasis and CFTR coupling, and its function is crucial for luminal fluid reabsorption in the male reproductive system [5].

Mutations in Adgrg2 have been associated with various male reproductive disorders. In humans, hemizygous loss-of-function mutations in Adgrg2 were identified as responsible for isolated congenital absence of vas deferens (CAVD) [2]. A novel nonsense mutation in Adgrg2 was found in infertile male patients of a Chinese pedigree, with members showing different genitalia phenotypes, and intracytoplasmic sperm injection (ICSI) had a low success rate in couples where the male had this mutation [4]. Also, a novel hemizygous mutation in Adgrg2 was reported in a patient with micropenis [3].

In conclusion, Adgrg2 is vital for male fertility, with its disruption leading to reproductive disorders such as CAVD, obstructive azoospermia, and micropenis. Studies on Adgrg2-related mutations in human patients help to understand its role in these disease conditions, providing insights into potential therapeutic strategies for male infertility and other associated disorders.