Increasing the grain yield of cereals, which is stable under unfavorable environmental stress, is a major objective to sustain production and feed the growing world population. Recently, we functionally characterized a receptor-like cytoplasmic kinase, named GROWTH UNDER DROUGHT KINASE (GUDK), revealing its role in regulating grain yield under well-watered and drought stress conditions by transphosphorylating the OsAP37 transcription factor. GUDK is induced under several stresses and its loss-of-function increased the sensitivity of rice seedlings to salinity, osmotic stress, and abscisic acid treatment. In addition to reduced tolerance of gudk mutant plants to drought stress at vegetative stage, a significant reduction in grain yield was observed under well-watered and drought stress conditions at reproductive stage. Gene co-expression analysis supports the role of GUDK in regulating important biological processes both under control and stress conditions. Thus, our results suggest that GUDK has the potential to regulate grain yield both under favorable and unfavorable conditions.