ANKLE2 and Familial prostate cancer: Gao et al., 2018 also showed that ANKLE2 facilitates phosphorylation of the tumor suppressor retinoblastoma protein (Rb), activating the cyclin D–CDK4–Rb signaling axis to promote tamoxifen resistance by sending the cell from G1 to S phase (Gao et al., 2018). For other cancers, such as prostate adenocarcinoma, LEM-domain-containing proteins – including ANKLE1, EMD and LEMD2 – can serve as prognostic markers. However, in this type of prostate cancer, no significant changes in ANKLE2 expression were found (He et al., 2022).