The first ORF encode a 500 amino acid - 40 kDa protein that lacks homology with any protein of known function. In vertebrates, it contains a conserved C-terminus domain and a highly variable coiled-coil N-terminus that mediates the formation of ORF1 trimeric complexes. ORF1 trimers have RNA-binding and nucleic acid chaperone activity that are necessary for retrotransposition. The second ORF of L1 encodes a protein that has endonuclease and reverse transcriptase activity. The encoded protein has a molecular weight of 150 kDA. L1 activity has been observed in numerous types of cancers, with particularly extensive insertions found in colorectal and lung cancers. It is currently unclear if these insertions are causal or secondary effects of cancer progression. However, at least two cases have found somatic L1 insertions causative of cancer by disrupting the coding sequences of genes APC and PTEN in colon and endometrial cancer, respectively. Quantification of L1 copy number by qPCR or L1 methylation levels with bisulfite sequencing are used as diagnostic biomarkers in some types of cancers. L1 hypomethylation of colon tumor samples is correlated with cancer stage progression. Furthermore, less invasive blood assays for L1 copy number or methylation levels are indicative of breast or bladder cancer progression and may serve as methods for early detection. Higher L1 copy numbers have been observed in the human brain compared to other organs. Studies of animal models and human cell lines have shown that L1s become active in neural progenitor cells (NPCs), and that experimental deregulation of or overexpression of L1 increases somatic mosaicism. This phenomenon is negatively regulated by Sox2, which is downregulated in NPCs, and by MeCP2 and methylation of the L1 5' UTR. Human cell lines modeling the neurological disorder Rett syndrome, which carry MeCP2 mutations, exhibit increased L1 transposition, suggesting a link between L1 activity and neurological disorders. Current studies are aimed at investigating the potential roles of L1 activity in various neuropsychiatric disorders including schizophrenia, autism spectrum disorders, epilepsy, bipolar disorder, Tourette syndrome, and drug addiction. Increased RNA levels of Alu, which requires L1 proteins, are associated with a form of age-related macular degeneration, a neurological disorder of the eyes. The naturally occurring mouse retinal degeneration model rd7 is caused by an L1 insertion in the Nr2e3 gene.