Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:10620060, PubMed:11028439, PubMed:14982838, PubMed:23942722, PubMed:33981039). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:19874193, PubMed:23942722, PubMed:33981039). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:9056646, PubMed:10620060, PubMed:11004006, PubMed:11028439, PubMed:12082181, PubMed:14982838, PubMed:32035618). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (PubMed:20684022, PubMed:26457330). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (PubMed:23427088). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:7550313). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (PubMed:19874193, PubMed:23942722, PubMed:23825434, PubMed:32028019). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (By similarity). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (PubMed:33981039). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (PubMed:33981039). a phosphate monoester + H2O = an alcohol + phosphate diphosphate + H2O = H(+) + 2 phosphate H2O + pyridoxal 5'-phosphate = phosphate + pyridoxal H2O + phosphoethanolamine = ethanolamine + phosphate H2O + N-phosphocreatine = creatine + phosphate ATP + H2O = ADP + H(+) + phosphate ADP + H2O = AMP + H(+) + phosphate AMP + H2O = adenosine + phosphate Binds 1 Mg(2+) ion. Binds 2 Zn(2+) ions. Phosphatase activity is specifically inhibited by 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425). Homodimer. Localizes to special class of extracellular vesicles, named matrix vesicles (MVs), which are released by osteogenic cells (PubMed:19874193, PubMed:23942722). Localizes to the mitochondria of thermogenic fat cells: tethered to mitochondrial membranes via a GPI-anchor and probably resides in the mitochondrion intermembrane space (PubMed:33981039). Widely expressed (PubMed:3478679). Expressed in DRG neurons and spinal cord neurons (PubMed:23825434). Not expressed prior to gastrulation in embryo, while it is expressed before in extraembryonic lineage cells destined to form the chorion (PubMed:7789278). Expressed in both embryonic and extraembryonic lineages during mouse embryogenesis (PubMed:7789278). By cold: up-regulated in response to cold both in brown and beige fat cells. Calcium-binding is structural and does not influence the alkaline phosphatase activity. At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity. N-glycosylated. Early death caused by defective metabolism of vitamin B6 (PubMed:7550313). At about two weeks of age, mice display seizures from which they die (PubMed:7550313, PubMed:9056646). Seizures are caused by a defect in the metabolism of pyridoxal 5'-phosphate (PLP) similar to that found in patients with hypophosphatasia, which ultimately results in a decrease in levels of 4-aminobutanoate (GABA) in the brain (PubMed:7550313). Mice do not show defects in skeletal formation during the first 8 days of life (PubMed:7550313, PubMed:10620060). Skeletal defects first appear at approximately 10 days of age and are characterized by worsening rachitic changes, osteopenia and fracture (PubMed:9056646, PubMed:10620060). Osteoblasts differentiate normally but are unable to initiate mineralization: histologic studies reveal developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones (PubMed:10620060, PubMed:11028439). Mineral crystals are initiated within matrix vesicles (MVs) of the growth plate and bone; however, mineral crystal proliferation and growth is inhibited in the matrix surrounding MVs, as in the case with hypophosphatasia (PubMed:14982838). Progressive osteoidosis from defective skeletal matrix mineralization is observed but not associated with features of secondary hyperparathyroidism (PubMed:10620060). Abnormal vitamin B6 metabolism is not the cause of impaired bone mineralization (PubMed:11169525). An accumulation of substrates is observed, characterized by strong elevation of urinary diphosphate (PPi) and phosphoethanolamine (PEA) levels and a striking accumulation of plasma PLP (PubMed:10620060). Mice lacking both Phospho1 and Alpl show a complete absence of skeletal mineralization, leading to perinatal lethality (PubMed:20684022). Bone mineralization in mice lacking both Enpp1 and Alpl is essentially normal, demonstrating that Enpp1 and Alpl are antagonist key regulators of bone mineralization by determining the normal steady-state levels of diphosphate (PPi) (PubMed:12082181). Conditional deletion in adipocytes leads to defective adaptive thermogenesis: defects are caused by abolition of the futile creatine cycle, thereby reducing whole-body energy expenditure and leading to rapid-onset obesity in mice, with no change in movement or feeding behavior (PubMed:33981039). In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP). Belongs to the alkaline phosphatase family.