Current treatments have changed cancer patients’ prognosis. However, cancer therapeutic resistance remains a major challenge accounting for approximately 10 million deaths in 2020. Therefore, there is an urgent need to identify more robust biomarkers that can be used as diagnostic/prognostic indicators and in turn as therapeutic targets. Since the last fifteen-years, Raf kinase inhibitor protein (RKIP) and Yin Yang 1 (YY1) emerged as interesting predictive molecules in cancer, cardiovascular disease, and diabetes. Their roles in chronic diseases are contradictory Therefore, the scientific committee of the present workshop has decided to integrate the most recent findings of these two gene products into a single conference. RKIP is a member of the phosphatidylethanolamine-binding protein (PEBP) family. It plays a pivotal modulatory role in several protein kinase signaling cascades. Cancer, heart disease and diabetes are leading causes of morbidity and mortality worldwide. These diseases have common risk factors, common molecular signaling pathways that are central to their pathogenesis, and even some disease phenotypes that are interdependent. Thus, the goal of therapeutic strategies should be to promote the normalization of these signaling pathways under pathological conditions. RKIP represents a physiological mechanism for achieving this outcome. YY1 is a crucial factor regulating cell proliferation and apoptosis and it has been implicated in many regulatory mechanisms in different tissues and particularly in cancer. YY1 overexpression is observed in many cancers and has various biological implications with respect to the hallmarks of cancer namely, YY1 suppresses the expression of a number of tumor suppressors involved in various cellular functions. The First International Conference on “Prognostic and Therapeutic Roles of Yin Yang 1 in Cancer” (Catania, Italy May 24-26, 2009) and The Second International Conference on “Prognostic and Therapeutic Applications of RKIP in Cancer” (Crete, Greece May 9-10, 2019) provided an excellent knowledge sharing a platform in the YY1 and RKIP fields. As the RKIP/YY1 fields continue to evolve, establishing novel cross-regulating networks, the organizers have decided to bring together a global think tank of scientists working either on YY1 or RKIP or both under the same roof, by organizing a joint RKIP/YY1 conference in Catania on March 2023. This conference will encompass keynote presentations by globally acclaimed speakers, panel discussions, and fireside chats in the hope to expand the frontiers of knowledge and stimulate dialogue on the recent advancements of YY1 and RKIP implications and targeting in cancer. Through this one-of-a-kind meeting, we further endeavor to offer a platform for networking and growth opportunities within an elite group of established individuals and young scientists who work on YY1 and/or RKIP.