The function of KLHDC2 (kelch domain containing 2, ENSG00000165516) is as follows. Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29775578, PubMed:29779948, PubMed:30526872, PubMed:36805027, PubMed:38177675). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29775578, PubMed:29779948, PubMed:30526872). The CRL2(KLHDC2) complex specifically recognizes proteins with a diglycine (Gly-Gly) at the C-terminus, leading to their ubiquitination and degradation (PubMed:29775578, PubMed:29779948, PubMed:30526872, PubMed:36805027, PubMed:38177675). The CRL2(KLHDC2) complex mediates ubiquitination and degradation of truncated SELENOK and SELENOS selenoproteins produced by failed UGA/Sec decoding, which end with a diglycine (PubMed:26138980, PubMed:30526872, PubMed:36805027). The CRL2(KLHDC2) complex also recognizes proteolytically cleaved proteins ending with Gly-Gly, such as the N-terminal fragment of USP1, leading to their degradation (PubMed:29775578, PubMed:30526872, PubMed:36805027, PubMed:38177675). May also act as an indirect repressor of CREB3-mediated transcription by interfering with CREB3- DNA-binding (PubMed:11384994). {ECO:0000269|PubMed:11384994, ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30526872, ECO:0000269|PubMed:36805027, ECO:0000269|PubMed:38177675}.