Alzheimer's disease (AD) is one of the most common forms of neurodegenerative disease. Amyloid-β peptide (Aβ) is the most crucial molecule related to the pathological development of AD. Amyloid-β protein precursor (AβPP) is one of AβPP family members with conserved type I transmembrane. The genetic mutations of AβPP and the abnormity of its post-transcription and proteolytic processing contribute to the elevation of Aβ. The accumulation of Aβ in senile plaques is believed to be the most important event in AD pathology. Therefore, as a key upstream molecule of Aβ, AβPP is related to the AD pathology, but the biological function of AβPP is still not fully clear. AβPP-like proteins are widely expressed in multicellular eukaryotes. AβPP-like homologous genes and proteins are highly conserved in various organisms from invertebrates to mammals. AβPP-like genes undergo similarly pathways of transcription and post-transcription processing, and AβPP-like proteins is proteolyzed by the similar α-cleavage and the β-cleavage pathways. Based on the homology and the resemble domains, AβPP may play similar roles in organisms. In this article, we reviewed homology and structures of AβPP family members in organisms and further discussed potential biological function in normal and AD brains.