THE GHRB subfamily is characterized by the broadest substrate selectivity and highest diversity in function among 2HADHs. Members of the GHRB clade use a large variety of postulated physiological substrates, as diverse as glyoxylate, hydroxypyruvate, phosphonate, ᴅ-mandalate, 2-keto-ᴅ-gluconate, phenylpyruvate, or 3,4-dihydroxyphenylpyruvate. At the same time, they exhibit a high level of promiscuity, i.e., accept various secondary substrates, which occasionally appear as the most efficient substrates for close homologs. As hydroxypyruvate and glyoxylate constitute important compounds in various metabolic pathways, GHRB members play crucial roles in many biological processes.