To address the contribution of the PRD domain to MORC2 functions in breast cancer development and progression, we generated a PRD domain deletion mutant of MORC2 (ΔPRD), and discovered that the PRD domain is dispensable for the stability and subcellular localization of MORC2, but is required for MORC2-mediated migration, invasion, and metastasis. Here, MORC2 is linked to breast cancer.