The human paracaspase Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) is a caspase homolog that is a key mediator of NF-κB signaling, promoting cell proliferation and survival.1 Scaffolding and proteolytic functions of the transcription factor both contribute to NF-κB signaling.2 As a scaffolding protein, MALT1 provides a platform for the assembly of NF-κB signaling proteins. As a protease, MALT1 proteolytically cleaves over a half dozen NF- κB antagonists.


MALT1 drives NF-κb expression in many cancers leading to enhanced cell survival and proliferation.3 MALT1 regulates NF-κb, but unlike NF-κb, is not essential for survival.

MALT1 plays a role in B-cell malignancies. 4,5

  • MALT1 is involved B-cell lymphocyte activation.
  • Specific B cell malignancies, including the aggressive non-germinal center B cell-like (GCB) subtype of diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), are driven by constitutive activation of NF-κB.

  1. Hachmann J, et al. The Paracaspase MALT1. Biochimie. 2016;122:324-38.
  2. Afonina IS, et al. MALT1-a universal soldier: multiple strategies to ensure NF-vB activation and target gene expression. FEBS J. 2015; 282(17):3286-97.
  3. Solsona BG, et al. The Paracaspase MALT1 in Cancer. Biomedicines. 2022;10(2):344.
  4. Yin W, et al. Identification of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies. Blood. 2020;136(1)30.
  5. Plotnik JP, et al. MALT1 protease inhibition overcomes BTK inhibitor resistance and shows synergistic activity with venetoclax in models of B-cell lymphoma and leukemia. AACR 2023. Poster 6156.