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Abstract: Parasporins (PSs), also known as delta endotoxins or Mammalian Pore-forming Proteins (Mpp), are non-hemolytic, non-insecticidal proteins secreted by Bacillus thuringiensis. They exhibit selective anticancer activities against various human tumor cell lines by recognizing and binding to specific cell membrane receptors. Currently, six PS families (PS1–PS6) have been identified in at least 11 B. thuringiensis strains. While distinct mechanisms have been proposed for some families (e.g., pore-formation by PS2, apoptosis induction by PS1), the precise molecular pathways for all families are not yet fully elucidated, and mechanistic overlap may exist. Through the exploration of established mechanisms-of-action (MOA) involving pore-forming proteins, significant alterations have been revealed, specifically in the permeability of the plasma membrane of their target cells, potentially culminating in cell death. The in vivo antitumor activity of PS proteins in animal models, such as mice and rats, remains relatively unexplored. This review aims to summarize the MOA of PS protein families produced by B. thuringiensis, evaluate research gaps in therapeutic development, in vivo efficacy, and the challenges of targeted delivery. Future perspectives and directions for harnessing these proteins as potential natural alternatives for cancer treatment are also highlighted.