PTIP regulates gene transcription by controlling the methylation of histone H3, and also has important roles in cellular responses to DNA damage or to perturbed DNA replication. The available data suggest that the functions of PTIP in transcription and preserving genome stability might be independent and mediated by functionally distinct cellular pools of PTIP. Although considerable progress has been made in understanding how PTIP influences transcription, a coherent picture of how it protects cells from DNA damage at the molecular level has yet to emerge. Here, we describe recent progress made in understanding the cellular roles of PTIP and the relevance of PTIP-interacting proteins, as well as the questions that have yet to be answered.