The MAPK/ERK pathway plays an important role in development and disease, with control over multiple cellular processes such as proliferation, differentiation and apoptosis, to name but a few. Despite its importance, little is known regarding its role in pituitary development and, specifically, in regulating the Sox2+ stem cell population therein. Now, on p. 2141, Scott Haston, from the Martinez-Barbera laboratory, and colleagues take a genetic approach to address the function of the MEK/ERK pathway during normal pituitary development, and relate this to human papillary craniopharyngioma (PCP), a form of benign but clinically relevant pituitary tumour. Using a MAPK gain-of-function mouse model, the authors demonstrate that constitutive activation of the MAPK/ERK pathway during pituitary development causes pituitary hyperplasia, abnormal morphogenesis and abnormal endocrine cell specification. This is due to sustained proliferation of the Sox2+ stem cell compartment, which results in an imbalance between proliferation and differentiation and, ultimately, an expansion of Sox2+ cells at the end of gestation. Looking at human PCP samples, the authors provide evidence that sustained proliferation of SOX2+ cells with reduced differentiation potential may contribute to the underlying pathogenesis of PCP. This study is an important step forward in understanding the role of the MAPK/ERK pathway in pituitary development, and sheds light on the possible pathogenesis of human PCP.