Mitochondrial 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide. (6S)-10-formyltetrahydrofolate + H2O + NADP(+) = (6S)-5,6,7,8-tetrahydrofolate + CO2 + H(+) + NADPH The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate. The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2. The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2. Phosphopantetheinylation at Ser-375 by AASDHPPT is required for the formyltetrahydrofolate dehydrogenase activity. Homozygous knockout mice lacking Aldh1l2 are viable and fertile and no embryonic lethality is observed (PubMed:33168096). They do not display phenotypic differences in terms of growth, food consumption and development (PubMed:33168096). 10-formyl-THF and dihydrofolate accumulate in the liver of the knockout mice. It is associated with a decrease in levels of NADPH and ATP specifically in the mitochondrion (PubMed:33168096). Male knockout mice accumulate more fats in the liver which is associated with impaired beta-oxidation of fatty acids (PubMed:33168096). In the N-terminal section; belongs to the GART family. In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.