PALB2 encodes a critical DNA repair protein that may be involved in tumour suppression. PALB2 functions by binding to and co-localizing with BRCA2, thereby permitting its stable intra-nuclear accumulation and preventing its proteasome-mediated degradation. The association of PALB2 with BRCA2 is critical as BRCA2 is essential for homologous recombination repair and tumour suppression. PALB2 also serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex.

Mutations in the PALB2 gene impair its function and therefore its ability to carry out DNA repair. This results in a build-up of inter-strand crosslinks ultimately stalling DNA replication and causing either abnormal cell death or uncontrolled cell growth. Abnormal cell death leads to blood cell shortage and manifests as Fanconi anaemia while uncontrolled cell growth develops into cancers. Hence, mutations in the PALB2 gene are associated with breast cancer, pancreatic cancer and Fanconi anaemia. Women with a PALB2 mutation have an almost ten times higher risk of breast cancer than average. PALB2 mutations are the second most common cause of hereditary pancreatic cancer and biallelic mutations in the PALB2 gene are associated with the Fanconi anemia complementation group N and an increased risk of early onset cancer.