EndNote 21

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Creating a Compressed Library:
Open your EndNote Library.
Go to File, then select Compress Library.
The Compress Library window will open.
Select your options and save.

EndNote, Reference Manager, & ProCite: Compatibility with Dropbox and other Cloud storage

Article Dropbox is a cloud based file sharing service. Our database products (EndNote, Reference Manager and ProCite) were not designed for compatibility with this service or other cloud storage. While you can use the service to keep a backup copy or share a compressed copy of your database file(s), we do not recommend opening and/or using the database from that location. If you have your database files saved to Dropbox or any cloud storage, we recommend you copy the files to another location on your computer or remote drive before you open them.

Storing EndNote libraries in cloud-syncing folders such as OneDrive, Box, iCloud, and others, or keeping read-write EndNote libraries on network drives or flash drives, will lead to an increased risk of library corruption. However, it is possible to put an EndNote library on a portable hard drive and use it with multiple computers. Use the File > Compress Library command to make backups of your libraries.

They explain further

20. How to work or share or transfer an EndNote library via cloud based storage service?
Each EndNote library consists of two items:

An .enl file (e.g., MyLibrary.enl)
An .Data folder (e.g., MyLibrary.Data)
The .Data folder consists of the (PDF) attachments and the database files and subfolders.

A compressed library consists of one .enlx file (e.g., MyLibrary.enlx, compare with .docx, .xlsx, .pptx). The .enlx file is in fact a zip-file. You can create a compressed library via EndNote menu 'File-Compressed Library'. It is optional whether you would like to include file attachments or not. The .enlx file is primarily for transfer purposes (email, usb stick).

Never store an EndNote working library (the .enl file and .Data folder) directly on any cloud service for sharing, or even just for your own use. Better copy your library file and folder to your local disk and open your library from the local disk. After you have finished your work, close the library and copy the files and folders back to the 'cloud' storage disk. Never create and save a compressed library directly to 'cloud' storage. Again, better save it to your local disk and copy the file to the 'cloud' storage. Else, this will eventually lead to library corruption because of the way the cloud services synchronize files over the Internet. Such unusable cloud services would include, but are not limited to:

Amazon Cloud
Box
Dropbox
Google Drive
Office 365
Sharepoint
OneDrive (formerly SkyDrive)
SugarSync
Similarly, never store a working library on a flash drive, for much the same reasons.
The reason these methods are inadvisable is that when you are working in EndNote, it is saving data to multiple files, and the data must be saved in a set sequence. When flash drives and cloud services transfer that data, they change the sequence of file saves to make the files transfer faster. This might eventually lead to library corruption.