Estrogen Receptor α (ERα), a member of the nuclear receptor superfamily of transcription factors, plays a central role in breast cancer development. More than two-thirds of patients with breast cancer are ERα-positive; however, a proportion becomes resistant. Phosphorylation of ERα is one of the mechanisms associated with resistance to endocrine therapy. In a kinome screen, we have identified the large tumor suppressor homolog-2 (LATS2) as a potential kinase, acting on ERα.The role of LATS2 on activation of ERα transcription and its functional consequences was examined by various molecular and cellular biology techniques.LATS2 co-localises with ERα in the nucleus. LATS2-silencing increases expression of ERα-regulated genes and inhibits proliferation. At the protein level, inhibition of LATS2 reduces the expression of cyclin-D1 and Nuclear Receptor Co-Repressor (NCoR) while increasing the expression of p27.Identifying novel kinases which modulate ERα activity is relevant to therapeutics. LATS2 modulates ERα-regulated gene transcription, through direct and/or indirect interactions with ERα.