Several phenotypes can come from transcription regulation. Sequence-specific transcription factors are needed to effectively execute transcriptional programs, however they are often not operating alone. Polycomb PcG proteins are a well-known class of chromatin regulators found in Drosophila melanogaster and other species, including humans. As time passed, the concept of a PCG gene or protein shifted from the original phenotypic meaning of mutant flies to the contemporary biochemical description. PCG genes and proteins are under investigation for their critical contributions to physiology and their cancer treatment potential. Adding additional PcG members, with substantial responsibilities in PRC modulation, has opened new routes of inquiry in the issue. It is still needed to discover the many PRC variations' roles and how their catalytic activity is controlled. This review covers mutually exclusive PRC2 variants and employs a technique like the one used for PRC1 variants. Based on current biochemical findings, these classifications are valid. More auxiliary PcG subunit research is needed for now. Moreover, it is unknown how many PRC cell variations occur (hypothetically, there could be more than 100 different PRC variants).In order to fully elucidate the new PcG proteins and complexes, it is necessary to perform comprehensive research. We must study context-specific genetic modifications to better provide remedies. Current anti-cancer drugs target mainly the core subunits and catalytic activity of PRC2 and PRC1, and understanding these functions is critical. Targeting each particular activity that has been deregulated might be rather beneficial. PCG proteins are involved in oncogenesis, tumor suppression, and development/congenital illness as well. PcG involvement in cancer, once revealed, would be intriguing. Successful and effective therapeutic therapies will be helped by a detailed understanding of the pathways that contain PcG proteins.