[7][9] Rhomboid family members share a conserved core of six transmembrane helices (TMHs), with the Ser and His residues required to form the catalytic dyad embedded in TMH-4 and TMH-6, respectively.

[7] Additionally, PARL is involved in apoptosis through its interactions with the mitochondrial GTPase optic atrophy 1 (OPA1) and the Bcl-2 family-related protein HAX1.

Alternatively, PARL can inhibit apoptosis by coordinating with HAX1 to activate HtrA2 protease, thus preventing the accumulation of the proapoptotic Bax.

[11] Variation in the sequence and/or expression of the gene encoding presenilins-associated rhomboid-like protein (PSARL) may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

[12] Mutations in PARL may also be involved in Leber hereditary optic neuropathy by disrupting normal function of the mitochondria, thus promoting retinal ganglion cell death and neurodegeneration.