Sad1 and UNC84 domain containing protein 5 (SUN5)

Sad1 and UNC84 domain containing protein 5 (SUN5, also known as SPAG4L, TSARG4, among other aliases) is a nuclear envelope protein primarily expressed in testis, localizing specifically at the sperm head–tail junction[4][5]. SUN5 plays an essential structural role in anchoring the sperm head to its tail, crucial for the formation of functional spermatozoa[2][3][4][5]. Loss-of-function mutations in SUN5 disrupt this tethering process, resulting in acephalic spermatozoa syndrome and consequent male infertility[3][5]. Besides its reproductive role, SUN5 is aberrantly upregulated in certain cancers (notably colorectal cancer), where it promotes cancer cell proliferation and migration via regulation of the ERK signaling pathway, acting through interaction with protein partners such as Nesprin2 and Nup93[1]. Thus, SUN5 may serve as both a biomarker and a potential therapeutic target in oncology[1]. No drugs currently target SUN5 directly, but its expression level can impact the efficacy of ERK pathway inhibitors in cancer settings[1].

Other names

SUN domain-containing protein 5SPAG4LTSARG4dJ726C3.1Sperm-associated antigen 4-like proteinTestis and spermatogenesis-related gene 4 proteintestis and spermatogenesis related gene 4SPGF16epididymis secretory sperm binding protein

Not applicable (no known drugs directly targeting SUN5); overexpression affects response to ERK pathway inhibitors in cancer[1]